Peripartum cardiomyopathy: A longitudinal echocardiographic study

Peripartum cardiomyopathy: A longitudinal echocardiographic study Andrea G. Witlin, DO, William C. Mabie, MD, and Baha M. Sibai, MD Memphis, Tennessee OBJECTIVE: Our purpose was to determine echocardiographic trends after initial diagnosis of peripartum cardiomyopathy.

STUDY DESIGN: Nine women diagnosed with peripartum cardiomyopathy were prospectively recruited for a longitudinal echocardiographic study. Severe myocardial dysfunction was defined as left ventricular end-diastolic dimension ->60 mm + fractional shortening -<21%, and mild dysfunction was defined as left ventricular end-diastolic dimension <60 mm + fractional shortening 22% to 24%. Unpaired t tests were used to compare sample means and Fisher's exact test used to compare discrete variables. RESULTS; All women were seen initially for pulmonary edema. Echocardiography showed decreased systolic function in all women. The mean age at diagnosis was 33.0 + 6.9 years. All but one woman had a diagnosis of either chronic hypertension (n = 6) or preeclampsia (n = 2). Four women were first seen ante partum and five post partum (range 1 day to 2 months). Repeat echocardiography was performed in all nine women (median 8 months, range 6 weeks to 5 years). There was no correlation between antepartum or postpartum presentation and cardiovascular status on follow-up (p = 0.3). Values for initial left ventricular end-diastolic dimension, severe versus mild dysfunction (68.3 _+ 7.2 mm vs 55.0 _+ 4.2 mm, p = 0.046), follow-up left ventricular end-diastolic dimension, severe versus mild (68.7 -+ 4.1 mm vs 52.0 _+ 5.7 mm, p = 0.002), and follow-up fractional shortening, severe versus mild (14.6% -+ 5.0% vs 28.5% _+ 9.2%, p = 0.02) are significant. Six of the seven women with severe dysfunction had stable disease in follow-up and one is awaiting heart transplant. One of the two women with mild dysfunction had disease resolution and one had stable disease. CONCLUSION: Patients with severe myocardial dysfunction due to peripartum cardiomyopathy are unlikely to regain normal cardiac function on follow-up. (Am J Obstet Gynecot 1997;177:1129-32.) Key words: Cardiomyopathy, pregnancy, echocardiography

Peripartum cardiomyopathy is an uncommon form of heart disease of unknown etiology. Estimates of the incidence vary from 1 in 1300 to 1 in 15,000 pregnancies. I' 2 In 1971 Demakis and Rahimtoola3 suggested the following criteria for peripartum cardiomyopathy: (1) onset of heart failure in the last month of pregnancy or in the first 5 months post partum, (2) absence of a determinable cause for cardiac failure, and (3) absence of demonstrable heart disease before the last month of pregnancy. A more favorable prognosis has been reported in women with periparrum cardiomyopathy as opposed to idiopathic dilated cardiomyopathy in age-matched controls34 In contrast, we have reported a dismal prognosis for women with periparturn cardiomyopathy; only two of 28 women (7%) had echocardiographic regression of disease. 5 From the Department of Obstetrics and Gynecology, University of Tennessee, Memphis. Presented at the SeventeenthAnnual Meeting of the Society of Perinatal Obstetricians, Anaheim, California,January. 20-25, 1997. Reprint requests: Andrea G. Witlin, DO, Department of Obstetrics and Gynecology, University of Texas Medical Center, 3,400 Old John Scaly/301 University Blvd., Galveston, TX 77555-0587. Copyright © 1997 by Mosby-Year Book, Inc. 0002-9378/97 $5.00 + 0 6/6/85028

The purpose of this study was to determine long-term echocardiographic trends and echocardiographic prognostic factors for women diagnosed with peripartum cardiomyopathy. Material and methods Between 1994 and 1996 women treated for or diagnosed with peripartum cardiomyopathy at the E.H. Crump Women's Hospital of the University of Tennessee, Memphis, were prospectively recruited for a longitudinal echocardiographic study. The longitudinal follow-up ranged from 6 weeks to 5 years and was performed in the echocardiographic laboratory. Institutional review board approval was granted before follow-up patient contact and subsequent echocardiographic studies. Included in the study were women with an echocardiographic diagnosis of dilated cardiomyopathy and systolic dysfunction. These women met the criteria for diagnosis of peripartum cardiomyopathy as outlined above. 3 Women with preexisting heart disease were excluded from consideration. Two-dimensional and Mmode echocardiography with continuous, pulsed, and color Doppler imaging was performed at the time of 1129

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November 1997 Am J Obstet Gynecol

T a b l e I. C a r d i o m y o p a t h y : P a t i e n t data

Patient No.

Age (yr)

Gestational age at delivery (wk)

1

34

40

Cesarean

Gestational diabetes

2 3 4 5

31 31 31 35

37 38 40 38

Vaginal Cesarean Cesarean Vaginal

Chronic hypertension Chronic hypertension Preeclampsia Chronic hypertension

6

20

33

Cesarean

Chronic hypertension

7 8

41 30

29 33

Vaginal Vaginal

9

44

34

Cesarean

Chronic hypertension Chronic hypertension, diabetes mellitns Preeclampsia

Mode of delivery

Associateddisorders

Presenting signs

Maternal outcome

4 days post partnm 36 wk 38 wk Recovery room 2 mo post partum 3 days post parmm 29 wk 16 wk

Shortness of breath, edema, cough Shortness of breath Shortness of breath Pulmonary edema Shortness of breath

Awaiting transplant Stable* Stable* Stable* Improved*

Chest pain

Stable*

Shortness of breath Shortness of breath

Stable* Stable*

1 day post partnm

Pulmonary edema

Stable*

Time of presentation

*Receiving triple therapy with digoxin, furosemide, and angiotensin-converting enzyme inhibitor. T a b l e II. E c h o c a r d i o g r a p h i c data

Left ventricular end-diastolic dimension (mnO Patient No. Women with severe dysfunction 1 2 3 4 6 7 8 Women with mild dysfunction 5 9

Fractional shortening (%)

Follow-up

Initial

Follow-up

Initial

Follow-up

6 wk 6 wk 8 mo 4 mo 5 yr 2 yr 7 mo

76 64 81 66 62 65 64

76 64 73 64 70 68 73

12 15 8 8 21 16 20

6 20 14 13 12 20 17

5 yr 3yT

58 52

56 48

22 23

22 35

initial diagnosis a n d d u r i n g follow-up. T h e left ventricular end-diastolic d i m e n s i o n a n d left v e n t r i c u l a r endsystolic d i m e n s i o n were m e a s u r e d as previously described by o u r g r o u p . 6 Left v e n t r i c u l a r dilatation was d e f i n e d as a left v e n t r i c u l a r end-diastolic d i m e n s i o n >-56 m m . Fractional s h o r t e n i n g was calculated as ([LVIDd] [LVIDs] + [LVIDd]) × 100, w h e r e LVIDd is left ventricular end-diastolic d i m e n s i o n a n d LVIDs is left v e n t r i c u l a r end-systolic d i m e n s i o n . Fractional s h o r t e n i n g < 2 5 % is c o n s i d e r e d a b n o r m a l in o u r laboratory. Mild myocardial dysfunction is d e f i n e d as left v e n t r i c u l a r end-diastolic d i m e n s i o n < 6 0 m m + fractional s h o r t e n i n g 22% to 24%; severe myocardial dysfunction is d e f i n e d as left v e n t r i c u l a r end-diastolic d i m e n s i o n > 6 0 m m + fractional s h o r t e n i n g ~<21%. U n p a i r e d t tests were u s e d to c o m p a r e sample m e a n s . Fisher's exact test was u s e d for discrete variables. A value o f p < 0.05 was c o n s i d e r e d significant. Values are rep o r t e d as m e a n + SD unless otherwise stated.

Results T h e study p o p u l a t i o n demographics, associated conditions, time of presentation, p r e s e n t i n g signs, a n d m a t e r n a l o u t c o m e s are summarized in Table I. All w o m e n were seen initially for p u l m o n a r y edema. T h e m e a n age at diagnosis was 33.0 _+ 6.9 years. All b u t o n e w o m a n h a d a diagnosis of either chronic hypertension (n = 6) or preeclampsia (n = 2). Four w o m e n were first seen a n t e p a r t u m a n d five post p a r t u m (range 1 day to 2 m o n t h s ) . E c h o c a r d i o g r a p h y s h o w e d d e c r e a s e d systolic f u n c t i o n in all w o m e n . R e p e a t e c h o c a r d i o g r a p h y was p e r f o r m e d in all n i n e w o m e n ( m e d i a n 8 m o n t h s , r a n g e 6 weeks to 5 years). T a b l e II s u m m a r i z e s t h e e c h o c a r d i o g r a p h i c data. Six o f t h e seven w o m e n with severe d y s f u n c t i o n h a d stable disease o n follow-up a n d o n e w o m a n is awaiting h e a r t t r a n s p l a n t . O n e o f t h e two w o m e n with m i l d dysfunction h a d disease resolution, a n d o n e w o m a n h a d i m p r o v e m e n t o f cardiac f u n c t i o n b o t h clinically a n d e c h o c a r d i o g r a p h i c a l l y yet r e q u i r e d triple t h e r a p y with

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Table III. Summary of echocardiographic data

Left ventricular end-diastolic dimension (ram) Systolic dysfunction Severe (n = 7) Mild (n = 2)

Fractional shortening (%)

Initial

Follow-up

Initial

Follow-up

68.3 + 7.2* 55.0 -+ 4.2

68.7 + 4.1" 52.0 -+ 5.7

14.3 -+ 5.3 22.5 + 0.7

14.6 -+ 5.0* 28.5 +- 9.2

*Values are significant when women with severe dysfunction are compared with women with mild dysfunction.

digoxin, furosemide, and angiotensin-converting enzyme inhibitor. There was no correlation between antepartum or postpartum presentation and cardiovascular status (i.e., disease resolution or clinical improvement vs persistent or progressive disease) on follow-up (p = 0.3). Table III provides a summary of the echocardiographic data by category of myocardial dysfunction. Values for initial and follow-up left ventricular enddiastolic dimension and follow-up fractional shortening are significant when the mean values for women with severe dysfunction are compared with the mean values for women with mild dysfunction. In those women having sequential echocardiographic studies, minimal echocardiographic change was identified after the initial pharmacologic therapy of the heart failure with digoxin, furosemide, and angiotensin-converting enzyme inhibitor. Patient 5 had a subsequent pregnancy during which she had decompensation with mild diffuse hypokinesis at 25 weeks' gestation. Comment

Historically, when dilated cardiomyopathy develops in the p e r i p a r t u m p e r i o d (as opposed to the nongravid state), the disease appears to r e g r e s s with greater frequency than with idiopathic dilated cardiomyopathy.l, ~, 4, 7-9 Approximately 50% of w o m e n have a return of h ear t size to normal within 6 to 12 months of the onset of the disease. 3 In contrast, we have r e p o r t e d progression or persistence of disease in 93% of women with peripartum cardiomyopathy. 5 In addition, our experience suggests that if a trend toward echocardiographic i m p r o v e m e n t is n o t identified after initiation of pharmacologic therapy (within 4 to 6 weeks), further significant echocardiographic i m p r o v e m e n t is not appreciated. This study attempts to define echocardiographic indicators of disease progression or regression. We found that none of the seven women with a left ventricular end-diastolic dimension ~60 mm and a fractional shortening <~21% regained normal cardiac function, whereas one of the two women with an initial left ventricular end-diastolic dimension <60 mm and an initial fractional shortening >21% had complete disease resolution. Perhaps those authors reporting a more favorable

prognosis for their patients with peripartum cardiomyopathy had a greater percentage of women who initially had mild disease. Alternatively, the diagnosis may have been incorrect in those earlier cases because it was based on clinical and radiographic findings rather than on echocardiography. Echocardiography should be the cornerstone for diagnosis of peripartum cardiomyopathy. Mabie et al. 6 have previously demonstrated the importance of echocardiographic findings in tailoring therapy in pregnant women with pulmonary edema. Electrocardiographic and chest x-ray examinations are nonspecific and not sensitive for the diagnosis of cardiomyopathy. Pharmacologic therapy for dilated cardiomyopathy should include an angiotensin-enzyme inhibitor because it has been shown to improve survival. 1°-12 Women with severe myocardial dysfunction (left ventricular end-diastolic dimension >-60 mm and fractional shortening ---21%) resulting from peripartum cardiomyopathy are unlikely to regain normal cardiac function on follow-up echocardiographic study. The preponderance of our patients presenting with and maintaining a similar degree of severe myocardial dysfunction on follow-up study may help explain the disparity between our findings and the literature. Absent clinical findings do not translate to absent clinical disease. Echocardiographic examination is necessary to differentiate disease state. In spite of the limited number of women studied in this report and the length of follow-up, we believe that our findings are potentially helpful for discussing longterm prognosis and for preconceptual counseling of women with peripartum cardiomyopathy. REFERENCES

1. Cunning'ham FG, Pritchard JA, Hankins GDV, Anderson PL, Lucas MJ, Armstrong KF. Periparmm heart failure: idiopathic cardiomyopathy or compounding cardiovascular events. Obstet Gynecol 1986;67:157-68. 2. DemakisJG, Rahimtoola SH, Sutton GC, Meadows R, Szanto PB, Tobin JR, et al. Natural course of peripartum cardiomyopathy. Circulation 1971;44:964-8. 3. Demakis JG, Rahimtoola SH. Peripartum cardiomyopathy. Circulation 1971;44:964-8. 4. Seftel H, Susser M. Maternity and myocardial failure in African women. Br Heart J 1961;23:45-52. 5. Witlin AG, Mabie WC, Sibai BM. Peripartum cardiomyopathy: an ominous diagnosis. AmJ Obstet G}aaecol 1997;176:182-8. 6. Mabie WC, Hackman BB, Sibai BM. Pulmonary edema

1132 Witlin, Mabie, and Sibai

associated with pregnancy: echocardiographic insights and implications for treatment. Obstet Gynecol 1993;81: 227-34. 7. O'ConnellJB, Costanzo-Nordin MR, Subranmanian R, Robinson JA, Wallis DE, Scanlon PJ, et al. Peripartum cardiomyopathy: clinical, hemodynamic, histologic and prognostic characteristics. J Am Coll Cardiol 1986;8:52-6. 8. Van Hoeven KH, Kitsis RN, ILatz SD, Factor SM. Peripartum versus idiopathic dilated cardiomyopathy in young women--a comparison of clinical, pathologic and prognostic features. Am J Cardiol 1993;40:57-65. 9. Sutton MSJ, Cole P, Plappert M, Saltzman D, Goldhaber S. Effects of subsequent pregnancy on left ventricular function

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in peripartum cardiomyopathy. Am Heart J 1991;121! 1776-8. 10. CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N EnglJ Med 1987;316:1429-35. 11. Cohn JN, Johnson G, Ziesche S, Cobb F, Francis G, Tristan F, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N EnglJ Med 1991;325:303-10. 12. SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N EnglJ Med 1991;325:293-302.

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